- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00052598
Therapeutic Allogeneic Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant
Phase I/II Study of Adoptive Immunotherapy With CD8+ Proteinase 3 (Myeloblastin)-Specific CTL Clones for HLA-A2+ Patients With Relapse or Progression of Disease After Allogeneic Hematopoietic Stem Cell Transplant for High Risk Myeloid Leukemias
Study Overview
Status
Conditions
- Recurrent Adult Acute Myeloid Leukemia
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
- Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
- Adult Acute Myeloid Leukemia With Del(5q)
- Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
- Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
- Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
- Secondary Acute Myeloid Leukemia
- Accelerated Phase Chronic Myelogenous Leukemia
- Childhood Chronic Myelogenous Leukemia
- Childhood Myelodysplastic Syndromes
- Recurrent Childhood Acute Myeloid Leukemia
- Relapsing Chronic Myelogenous Leukemia
- Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
- Blastic Phase Chronic Myelogenous Leukemia
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the safety and potential toxicities associated with infusing donor CD8+ cytotoxic T lymphocytes (CTL) clones specific for Proteinase 3 (Myeloblastin) in patients with relapse/progression of high risk myeloid leukemias after transplant.
SECONDARY OBJECTIVES:
I. To determine the in vivo persistence of transferred T cells and assess migration to the bone marrow, a predominant site of leukemic relapse.
II. To determine if adoptively transferred proteinase 3 (PR3)-specific T cells mediate antileukemic activity.
OUTLINE:
Patients receive allogeneic CD8+ PR3-specific CTLs intravenously (IV) over 1-2 hours on days 0, 7, 14, 28, and 49 and aldesleukin subcutaneously (SC) twice daily on days 28-41 and 49-63 in the absence of unacceptable toxicity.
After completion of study treatment, patients are followed up every 1-3 months.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients undergoing allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia (CML) in accelerated or blast phase, acute myeloid leukemia (AML) beyond first remission, primary refractory AML, therapy-related AML at any stage, or acute leukemia at any stage arising in a patient with an antecedent diagnosis of a myelodysplastic or myeloproliferative syndrome (including chronic myelomonocytic leukemia, CML, polycythemia vera, essential thrombocytosis, and agnogenic myeloid metaplasia with myelofibrosis)
- Patients and donors must both be human leukocyte antigen (HLA)-A2 positive
- Patients must be able to provide blood and bone marrow samples required for this protocol
- Eligibility for Prophylactic Treatment with CD8+ CTL After Transplant (Highest Risk Subgroup):
- At time of planned treatment, CD8+ CTL specific for PR3 must have been generated and have completed Quality Control (QC) testing
- Patients must have had > 5% morphologic blasts detectable in bone marrow or peripheral blood just prior to or at the time of transplant
- Patients must have evidence of posttransplant recovery of normal hematopoiesis (absolute neutrophil count [ANC] > 500/mm^3) for at least 7 days prior to the initiation of CTL infusions
- Patients on immunosuppressive therapy for graft-versus-host disease (GVHD) are eligible for treatment if not receiving corticosteroids or if the dose of corticosteroids can be tapered to < the equivalent of 0.5 mg/kg/day of prednisone; The patient's symptoms have to remain stable and unlikely to increase to stage III or IV acute GVHD or chronic GVHD is unlikely to progress following the change in immunosuppressive therapy, after an appropriate monitoring period, as deemed by the patients treating physician and the principal investigator
- Eligibility for Treatment with CD8+ CTL at the Time of Relapse After Transplant (All Others):
- At time of planned treatment, CD8+ CTL specific for PR3 must have been generated and have completed Quality Control (QC) testing
- Patients must have evidence of recurrent/progressive disease posttransplant
- Morphologic relapse defined as one or more of the following: abnormal peripheral blasts in absence of growth factor therapy, abnormal bone marrow blasts > 5% of nucleated cells, extramedullary chloroma or granulocytic sarcoma
- Flow cytometric relapse defined as the appearance in the peripheral blood or bone marrow of cells with an abnormal immunophenotype detected by flow cytometry that is consistent with leukemia recurrence/progression
- Cytogenetic relapse/progression defined as the appearance in one or more metaphases from bone marrow or peripheral blood cells of either a non-constitutional cytogenetic abnormality identified in at least one cytogenetic study performed prior to transplant or a new abnormality known to be associated with leukemia; (for CML), an increase in the number of Ph+ metaphases from bone marrow or peripheral blood between two consecutive samples after engraftment, or an increase in the percentage of BCR/ABL+ cells by fluorescence in situ hybridization (FISH) between two consecutive samples after engraftment
- Molecular relapse/progression defined as a polymerase chain reaction (PCR) assay of bone marrow (BM) or peripheral blood mononuclear cells (PBMC) positive for the presence of the BCR/ABL messenger ribonucleic acid (mRNA) fusion transcript that quantitatively increases by greater than one order of magnitude on a subsequent sample
- Patients on immunosuppressive therapy for GVHD at the time of relapse are eligible for treatment if not receiving corticosteroids or if the dose of corticosteroids can be tapered to < the equivalent of 0.5 mg/kg/day of prednisone; the patient's symptoms have to remain stable and unlikely to increase to stage III or IV acute GVHD or chronic GVHD is unlikely to progress following the change in immunosuppressive therapy, after an appropriate monitoring period, as deemed by the patient's treating physician and the principal investigator
Exclusion Criteria:
- Exclusions for Treatment at the Time of Relapse/Progression After Transplant:
- Patients for whom CD8+ CTL clones specific for PR3 have not been generated by the time of disease relapse/progression post-transplant; these patients can potentially be treated later if CTL become available; patients whose malignant cells do not overexpress PR3, based on direct analysis of a bone marrow sample with > 50% blasts or of leukemia cells isolated for expression analysis; in either case, patients will be informed about the availability of other treatment protocols for which they might be eligible
- Patients with Karnofsky performance status or Lansky play score =< 30%
- Patients with current stage III or IV GVHD unresponsive to therapy or requiring therapy with anti-CD3 mAb, prednisone > 0.5 mg/kg/day (or corticosteroid equivalent), or other treatments resulting in the ablation or inactivation of T cells (such as other anti-T cell monoclonal antibodies); although the concurrent use of cyclosporine, FK506, or mycophenolate mofetil (MMF) is not strictly an exclusion criterion, attempts should be made to discontinue it if possible
- Patients requiring concurrent therapy with hydroxyurea or other agents that may interfere with the function or survival of infused CTL clones
- Patients with a preexisting nonhematopoietic organ toxicity that is deemed by the principal investigator to place the patient at unacceptable risk for treatment on the protocol
- Patients with graft rejection or failure
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (adoptive immunotherapy)
Patients receive allogeneic CD8+ PR3-specific CTLs IV over 1-2 hours on days 0, 7, 14, 28, and 49 and aldesleukin SC twice daily on days 28-41 and 49-63 in the absence of unacceptable toxicity.
|
Correlative studies
Correlative studies
Given SC
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Toxicity rate associated with infusing donor CD8+CTL clones specific for PR3
Time Frame: From the first CTL infusion to 4 weeks after the final dose of CTL or IL-2
|
From the first CTL infusion to 4 weeks after the final dose of CTL or IL-2
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
In vivo persistence of transferred T-cells and assessment of migration to the bone marrow
Time Frame: Baseline and days +7, +11, +14, +21, and +28 after each CTL infusion
|
Baseline and days +7, +11, +14, +21, and +28 after each CTL infusion
|
Duration of response as assessed by PCR or cytogenetic analysis of peripheral blood and bone marrow samples
Time Frame: Days +0, +15, +29, +50, +63, and at approximately 1 month after completion of all therapy
|
Days +0, +15, +29, +50, +63, and at approximately 1 month after completion of all therapy
|
Proportion of responders
Time Frame: Approximately one month after completion of all therapy
|
Approximately one month after completion of all therapy
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Gunnar Ragnarsson, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease Attributes
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Neoplastic Processes
- Precancerous Conditions
- Cell Transformation, Neoplastic
- Carcinogenesis
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Recurrence
- Preleukemia
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Blast Crisis
- Leukemia, Myeloid, Accelerated Phase
- Physiological Effects of Drugs
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Anti-HIV Agents
- Anti-Retroviral Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antineoplastic Agents
- Aldesleukin
- Interleukin-2
Other Study ID Numbers
- 1671.00
- P01CA018029 (U.S. NIH Grant/Contract)
- NCI-2010-00826 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Adult Acute Myeloid Leukemia
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) | Adult Acute Myeloid Leukemia in Remission | Childhood Acute Myeloid Leukemia in Remission | Recurrent... and other conditionsUnited States
-
Alison WalkerCompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) | Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) | Adult Acute Myeloid Leukemia With t(8... and other conditionsUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)Approved for marketingRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) | Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) | Adult Acute Myeloid Leukemia With t(8... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) | Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) | Adult Acute Myeloid Leukemia With t(8... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Recurrent Adult Acute Lymphoblastic Leukemia | Untreated Adult Acute Lymphoblastic LeukemiaUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid LeukemiaUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Untreated Adult Acute Myeloid LeukemiaUnited States
-
National Cancer Institute (NCI)TerminatedRecurrent Adult Acute Myeloid Leukemia | Untreated Adult Acute Myeloid LeukemiaUnited States
-
University of Colorado, DenverThe Leukemia and Lymphoma SocietyCompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia in RemissionUnited States
-
Bhavana BhatnagarCTI BioPharmaCompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
Clinical Trials on laboratory biomarker analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States